Current Stem Cell Research & Therapy - Volume 8, Issue 6, 2013

Tissue engineering and cell therapies are currently being leveraged to find improved treatment strategies in orthopaedics. Adipose stem cells have been considered for their potential to differentiate into different cell lineages. The potential of adipose stem cells to restore chondral, bone and tendon tissue has been demonstrated in vivo and in vitro studies. Recently their capacity to restore cells and extracellular matrix of the intervetebral disc has been also investigated. Treatment of several orthopedic diseases could benefit from the application of adipose stem cells. However, there is still lack of knowledge about their clinical use and further studies are needed to better clarify their potential.

Knee injuries involving ligament, articular cartilage and meniscus are common. The capacity for regeneration and repair of these tissues is limited due to their poor vascularity. Autologous or allogeneic stem cell transplantation has the potential to stimulate healing of these tissues. A number of preclinical studies of stem cell therapy for repair of these injuries have produced promising results. Further clinical trials are needed to test the efficacy of this technique. This paper reviews the development strategies, advances and clinical applications of stem cell therapies that are applicable to knee ligament, articular cartilage and meniscal injuries.

Several artificial biomaterials are available as ligament grafts. No ideal prosthesis mimicking natural human tissue have been found to date. The emerging field of tissue engineering holds the promise to use artificial ligaments as a viable alternative to the patellar or hamstring tendon autografts. Preliminary studies support the idea that these biomaterials have the ability to provide an alternative for autogenous grafts. However, no definitive conclusions have been found. Additionally, the incidence of postoperative complications varies within different studies. Prospective investigations are required to better understand the potential of artificial biomaterials as ligament grafts.

The emerging field of tissue engineering holds the promise to use bio-materials for meniscus injury repair, namely scaffold or meniscus implant. Many implants have been studied and several studies have been conducted to verify the safety and quality of scaffolds. Preliminary data support the idea that synthetic implants can provide an alternative to menyscectomy helping to preserve the cartilage and preventing arthritis in patient with menisci injuries. However, the prevalence of postoperative complications varies within studies. Further investigations are required to evaluate the role of these materials in the clinical practice.

Joint diseases are a major cause of disability and are a significant financial burden on health care systems. Regenerative medicine offers exciting possibilities for treating osteoarthritis and rheumatoid arthritis. As well as possessing the ability to differentiate into other tissue lineages, some stem cells such as mesenchymal stem cells possess immmunomodulatory properties that make them useful in the search for alternative treatments for rheumatoid arthritis specifically. Various studies have been carried out using animal models to evaluate the role of stem cells in the treatment of arthritis, with some research being translated into clinical studies. However, the number of patients used in some studies has left questions on the ability of stem cell therapy to treat arthritic conditions unanswered. This article reviews the innovative studies that have been carried out to treat arthritis using stem cells and also highlights the key challenges associated with these techniques.

Physeal injuries may lead to the formation of a bone bridge resulting in limb length discrepancies and angular deformity in children. Current treatment of physeal injuries may be challenging. A number of strategies have been used to repair physeal defects with varying results. Biological regeneration using stem cells is therefore an attractive potential future option to repair physeal defects. Preclinical animal studies using stem cells have shown mixed results. Studies have investigated the use of various scaffolds including chitin, collagen and gelfoam. Significant progress has been made in discovering appropriate growth factors such as transforming growth factor (TGF-β), insulin-like growth factor (IGF-1), bone morphogenetic proteins (BMPs) and fibroblast growth factor (FGF-2) that could induce physeal repair and be used in combination with stem cell therapy. Advances have been made in the use of gene therapy to maintain sustainable delivery of growth factors to injury sites. This review discusses the current stem cell therapy available to repair physeal injuries.

Spinal pathologies are a major burden on society and individuals. Recent years have seen a large number of studies dedicated to the use of stem cells in spinal surgery. This review focuses on recent advances and controversies regarding the applications of stem cells in spinal fusion surgery, spinal cord injury and intervertebral disc degeneration. There are significant concerns regarding the ethics and risks of stem cell use. Animal models do not always accurately depict the human condition. While a great deal has been achieved, successful translation into clinical practice is needed. However there is no doubt that stem cells have a major role to play in the future management of spinal conditions.

Rotator cuff tear causes a high rate of morbidity. After surgical repair, the presence of a scar tissue reduces tendon biomechanical properties. Emerging strategies for enhancing tendon healing are growth factors, cytokines, gene therapy and tissue engineering. However their efficacy has to be proved. Growth factors help the process of tendon healing by aiding cells chemotaxis, differentiation and proliferation. Numerous growth factors, including the bone morphogenetic proteins and platelet-derived growth factor can be found during the early healing process of a rotator cuff repair. Growth factors are delivered to the repair site using tissue-engineered scaffolding, coated sutures, or dissolved in a fibrin sealant. Platelet-rich plasma is an autologous concentration of platelets and contains an high density of growth factors. There is some evidence that platelet-rich plasma may improve pain and recovery of function in a short time period, but it does not improve healing rates in rotator cuff. Thus the routine use of platelet-rich plasma in rotator cuff repair is not recommended. The addition of mesenchymal stem cells to scaffolds can lead to the production of a better quality healing tissue. Gene therapy is a gene transfer from a cell into another, in order to over-express the gene required. In this way, cultures of stem cells can over-express growth factors. Better understanding of the mechanisms of physiological tendon healing can promote the correct use of these new biological therapies for a better healing tissue.

Diabetes mellitus (DM) is considered to be an autoimmune disorder leading to destruction of beta-cells resulting in to a loss of blood sugar control. Attempts using many pharmacological compositions including exogenous insulin have failed to show tight control of glycemia and associated manifestations. Stem cells are considered a potential tool for the supply of insulin-producing cells (IPC) generation in vitro. Stem cell differentiation in to pancreatic lineages requires influence of both intrinsic and extrinsic factors. Application of islet growth factors is considered to be potential for enhancement of beta-cell replication, function and survival. Use of certain extrinsic factors is known to facilitate expression of transcription factors known to be important for beta-cell differentiation and production of insulin enabling IPC generation. Hierarchies of secreted signals and transcription factors have been identified by studies from several laboratories that guide cell differentiation in to IPC. This knowledge provides insights for in vitro IPC differentiation from stem cells. Current advancement in medical knowledge promises an insulin independency for DM patients. The review sheds light on few specific extrinsic factors which facilitate differentiation of stem cells in to IPC in vitro have been discussed; which can be proven as a potential therapeutic option for treatment of DM and associated diseases.